Objective To evaluate the efficacy of mitomycin (MMC) intravesical chemotherapy for superficial bladder carcinoma by in vitro chemosensitivity using histoculture drug response assay (HDRA).Methods Forty-one cases of superficial bladder transitional cell carcinoma(TCC) were obtained,including 30 males and 11 females with mean age of 55 years.Of them,10 cases were Ta and 31 were T1 according to TNM stage system (UICC 2002) while 9 cases were G1,22 were G2 and 10 were G3 (WHO1973).All cases had no chemotherapy history before operation and were operated to retain bladder.Tumor specimens were cultured by three-dimensional histoculture.HDRA with im-proved MTT assay was utilized for chemosenstivity test of MMC with 1 g/L concentration and 2 hours exposure.Growth inhibition rate (GI) exceeding 70% was defined as high-sensitive while less than 50% GI was defined as insensitive,others were moderate-sensitive.All cases were performed standard intravesical chemotherapy with MMC 40 mg plus 40 mt saline.Every case was followed up every 3 months.The patients were followed up for 5 years or untill recurrence.Results The MMC chem-osensitivity was different among 41 patients.Thirteen cases were insensitive including 1 of Ta,12 of T1 (P=0.009) and 1 of G1,7 of G2,5 of G3(P=0.101).Total recurrence rate was 39%(16/41) af-ter 3 to 5 years follow-up.There were 1 of Ta,15 of T1 (P=0.059) and 10 of G2 6 of G3 (P=0.016).Insensitive group recurrence rate was 77% (10/13) while sensitive group was 21% (6/28,P= 0.004).Patients in sensitive group showed a longer median time(49.2 months) than patients in insen-sitive group (16.5 months,P<0.001) according to Kaplan-Meier analysis with Log-rank test.The MMC chemosensitivity was independent prognostic factor examed by Cox regression analysis (P= 0.008).There was a 78% correlation rate of chemosensitivity by HDRA to clinical effect of MMC in-travesical chemotherapy.Conclusion HDRA could evaluate MMC intravesical chemotherapy for su-perficial bladder TCC,improve therapeutic effect and lower tumor recurrence rate.

Objective To study the application of pediculated skin flaps in the treatment of com-plicated long urethratresia. Methods From March 1999 to May 2006, a total of 18 male patients with complicated long urethratresia were treated by using the pediculated skin flaps. The causes of urethratresia were 7 cases of postoperative pelvic fractures with posterior urethral stricture, 4 cases of transurethral intravesical chemotherapy, 3 cases of postoperative bulbar urethral stricture, 2 cases of gonorrhea, and 2 cases of long-time urethral catheter placement. Four cases were urethratresia nf cor-pus penis, 7 cases were anterior urethral obliteration, 7 cases were posterior urethral and anterior ure-thral obliteration. Urethro-perineal fistulas were found in 8 cases, posterior urethrorectal fistulas in 7 cases, false passage formations in 8 cases. The average length of urethratresia was 15.1 cm (range 8. 7 to 23. 0 cm). The urethral scar was rasected, the posterior urethrorectal fistula was repaired, and different kinds of pediculated skin flaps depending on the length of urethratreaia was used. Results All the patients were followed up for 12 to 18 months (mean 14 months). Fifteen patients voided well 3 months postoperatively, none of the urography showed stricture. The mean peak urinary flow rate was 16. 9 ml/s (range from 16. 5 to 21.7 ml/s). Of the other 3 cases, 1 case experienced difficult voi-ding due to the long and circuitous tabularized skin flap but recovered after proper shortening;1 case had restenosis for the infection of anastomosis but voided well after excision and reanastomnsis;1 casehad a urinary fistula resulting from hematoma and infection, but was successfully treated by the neo-plasty of the urinary fistula. The mean peak urinary flow rate was 17.0 ml/s (range 15.0 to 22.0 ml/s) for 17 patients 6 months postoperatively, except for one who experienced genuine urinary incon-tinence. At 9-18 months after operations, the mean peak urinary flow rate was 17.5 ml/s (range 15.8 to 22.5 ml/s) for 17 patients. Conclusion The single-stage urethroplasty based on pediculated skin flaps is a reliable and durable method for complicated long urethratresia.

Objective To explore the effect of Linc00460 on the aerobic glycolysis of breast cancer (BC) cells through sponge adsorption of miR-320a. Methods The qRT-PCR method was used to detect Linc00460 and miR-320a expression levels in normal breast epithelial cell line MCF-10A and five BC cell lines. The effect of interfering Linc00460 on miR-320a expression was detected by qRT-PCR. The double luciferase reporter gene experiment was used to analyze the targeting relationship between miR-320a and Linc00460. In addition, the si-Linc00460 and miR-320a inhibitor were co-transfected into MDA-MB-231 cells, and the expression level of miR-320a in the cells was detected by qRT-PCR; cell proliferation ability was measured by the MTT method; glucose uptake rate was detected by 2-NBDG method; the content of lactic acid in the cell supernatant was detected by colorimetric method; the key enzymes of glycolysis was detected by the enzyme activity kit; and the expression levels of the key proteins in the glycolysis pathway were detected by Western blot. Results Linc00460 was highly expressed in five BC cell lines, while miR-320a was lowly expressed as compared with MCF-10A cells. The expression of miR-320a in MDA-MB-231 cells significantly increased after interfering with Linc00460. The double luciferase reporter gene experiment confirmed that miR-320a and Linc00460 could target binding. Interfering with the expression of Linc00460 could inhibit MDA-MB-231 cells proliferation (all P=0.000), reduce the rate of cellular glucose uptake and the content of lactic acid in the cell supernatant (all P=0.000), inhibit the activities of PFK, PK, and LDH enzymes (all P=0.000), and downregulate the protein expression levels of PFKM, GLUT1, and LDHA (all P=0.000). Meanwhile, inhibition of miR-320a could reverse the inhibitory effect of si-Linc00460 on the proliferation and glycolysis of MDA-MB-231 cells (all P=0.000 or 0.001). Conclusion Linc00460 might adsorb miR-320a, consequently leading to upregulation of PFKM expression, thereby promoting aerobic glycolysis in BC cells.

Objective:To explore the efficacy and safety of tislelizumab combined with zanubrutinib in the treatment of refractory diffuse large B-cell lymphoma (DLBCL).Methods:A prospective observational study was conducted. A total of 10 patients with refractory DLBCL admitted to Beijing Chaoyang District Third Ring Cancer Hospital, a specialist medical consortium of Cancer Hospital Chinese Academy of Medical Sciences from November 2020 to February 2023 were prospectively collected. All the 10 refractory DLBCL patients at least received first-line systemic therapy containing rituximab; and they were given tislelizumab 200 mg, intravenous infusion, on day 1 and zanubrutinib 160 mg, orally, twice a day, day 1-day 21, with 21 days as 1 cycle; 6 patients received second-line therapy and 4 patients received ≥ third-line therapy. Subsequent regimens were added with rituximab (375 mg/m 2, intravenous infusion on day 1). The primary endpoint will be reached 12 months after enrollment if there was no disease progression or other events that were scheduled to withdraw from the study. The therapeutic efficacy was summarized at the end of the follow-up in March 2023. Kaplan-Meier method was used to make survival analysis and the adverse reactions were summed up. Results:There were 6 males and 4 females, all at stage Ⅲ-Ⅳ; and age [ M ( Q1, Q3)] was 55 years (50 years, 69 years). All 10 patients completed 90 cycles of treatment with tislelizumab and zanubrutinib, with the cycle number of 8 cycles (2 cycles, 24 cycles). The follow-up time was 19 months (11 months, 28 months); 4 cases achieved complete remission, 3 cases achieved partial remission and 1 case had the stable disease. The progression-free survival was 8.5 months (1.3 months, 27.0 months); the median remission duration time and median overall survival time were not reached. Treatment-related adverse reactions included 2 cases of neutropenia, 1 case of anemia, and 1 case of elevated alanine aminotransferase and aspartate aminotransferase, all of which were grade 1-2. Conclusions:Tislelizumab combined with zanubrutinib has good clinical efficacy and safety in the treatment of refractory DLBCL.